This Core serves two functions. The first is to provide a service to other TCORS investigators by carrying out the analysis of biofluid samples for their studies. The second is to develop new biomarkers of exposure that can be applied to the studies carried out by TCORS investigators, as well as to advance the field. Our laboratory is able to measure alkaloids and toxic substances in both tobacco products and in tobacco smoke. These measurements are needed for biomarker development and to interpret the biomarker data for distinguishing smokeless from smoked tobacco use. These measurements will include other substances in order to explore relationships between toxins and toxin precursors in tobacco and smoke with exposure determined using biomarkers. The improved exposure assessment measures that we expect to develop, and their application to studies carried out by the TCORS, could serve as models for future studies of the risks of new tobacco products and provide scientific basis for their regulation. RELEVANCE (See instructions): The development and validation of biomarkers is a high priority issue for FDA regulation. Studies of tobacco product chemistry with biomarker analyses may provide information on which substances are associated with toxin exposure in humans. Precursors in smoking products that generate toxic substances might provide leads for reducing the toxicity of new products or be targets for regulation. We expect that our studies will result in improved methods for determining human exposure to toxic substances in tobacco and tobacco smoke.